Proteomics-based approach to ARDS

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DESCRIPTION (provided by applicant): Adult Respiratory Distress Syndrome (ARDS) is a devastating process of rapidly progressive and severe respiratory failure. ARDS is characterized by an acute inflammatory process with damage to the epithelial and endothelial barrier. Our current understanding of the basic pathogenic mechanisms involved in lung injury is incomplete. Our ability to predict the onset of lung injury in patients at risk and the severity of lung injury once it develops is poor. Efforts to identify cellular and/or biochemical markers for outcomes in serum or bronchoalveolar lavage fluid (BALF) has shown that single biochemical measurements are not consistent predictors of either the onset or the severity of ARDS. This approach fails to identify unsuspected mediators or new proteins. The goal of this proposal is to obtain global protein profiles of the airspace environment during ARDS by analyzing BALFobtained as part of the Seattle ARDS SCOR Program in acute lung injury. New methodologies in proteomics, such as isotope-coded affinity tag, and automated validation process, will be used to analyze BALF. These techniques enable one to obtain quantitative and qualitative protein analysis of complex biological specimens, and can be performed with a high throughput facility. The obtained protein profiles will be used to develop classification schemes that will assist in predicting outcome and assist in therapeutic decisions. Additionally, novel or unsuspected mediators and regulatory pathways involved in the development of ARDS may be discovered and may verify or challenge mechanisms of ARDS. Finally, any generated models and hypothesis will tested prospectively in ARDS patients during the continuation of the acute lung injury program. The goals of this study are to: 1. Examine the protein profile of BALF from day 3 ARDS patients, compared to normals in order to identify the spectrum of soluble proteins present in ARDS BALF and potentially identify new proteins. 2. Analyze the protein profiles from serial samples from the same patients in order to obtain a time course of protein expression during the development of ARDS. 3. Compare protein profiles from at risk that progressed to ARDS versus at risk with no progression. 4. Compare protein profiles from ARDS survivors vs. ARDS non-survivors. These results will be used to develop prediction models for the outcome of lung injury.